Single point mutations induce a switch in the molecular mechanism of the aggregation of the Alzheimer's disease associated Aβ42 peptide.

Abstract

Single point mutations in the Alzheimer's disease associated Aβ42 peptide are found to alter significantly its neurotoxic properties in vivo and have been associated with early onset forms of this devastating condition. We show that such mutations can induce structural changes in Aβ42 fibrils and are associated with a dramatic switch in the fibril-dependent mechanism by which Aβ42 aggregates. These observations reveal how subtle perturbations to the physicochemical properties of the Aβ peptide, and the structural properties of fibrils that it forms, can have profound effects on the mechanism of its aggregation and pathogenicity.

• Authors: Benedetta Bolognesi, Samuel I A Cohen, Pablo Aran Terol, Elin K Esbjörner, Sofia Giorgetti, Maria F Mossuto, Antonino Natalello, Ann-Christin Brorsson, Tuomas P J Knowles, Christopher M Dobson, Leila M Luheshi
• Journal: ACS chemical biology (ACS Chem Biol) Vol. 9 Issue 2 Pg. 378-82 (Feb 21 2014) ISSN: 1554-8937 [Electronic] United States
• PMID: 24199868 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Peptide Fragments
• amyloid beta-protein (1-42)

Topics

• Alzheimer Disease (genetics, metabolism, pathology)
• Amyloid beta-Peptides (genetics, metabolism, ultrastructure)
• Humans
• Microscopy, Atomic Force
• Peptide Fragments (genetics, metabolism, ultrastructure)
• Point Mutation
• Spectroscopy, Fourier Transform Infrared